Search results for "Phosphodiesterase Inhibitors"
showing 10 items of 65 documents
Selective Inhibition of Phosphodiesterases 4A, B, C and D Isoforms in Chronic Respiratory Diseases: Current and Future Evidences
2016
Chronic respiratory diseases affect millions of people every day. According to the World Health Organization estimates, ~235 million people suffer from asthma, ~64 million suffer from chronic obstructive pulmonary disease (COPD), and millions more suffer from allergic rhinitis around the world. In recent last years, the first phosphodiesterase 4 (PDE4) inhibitor, roflumilast, was approved as a treatment to reduce the risk of exacerbations in stable and severe COPD associated with chronic bronchitis and a history of exacerbations. PDE4 exists as four subtypes (A, B, C, and D) each with a capacity to degrade cAMP, a second messenger involved in inflammatory responses. PDE4 inhibitors inhibit …
Pentoxifylline Inhibits Vγ9/Vδ2 T Lymphocyte Activation of Patients with Active Behçet's Disease in Vitro
2007
The aim of this study is to evaluate the in vitro effect of pentoxifylline (PTX) on T Vgamma9/Vdelta2 lymphocyte function in Behçets disease (BD). We investigated the effect of PTX on Vgamma9/Vdelta2 T cell expansion and expression of TNFRII receptor and perforin content before and after PTX addition by means of FACS analysis lymphocyte cultures from patients with active and inactive BD and healthy subjects. The addition of PTX at a concentration of 1 mg/ml determined a significant inhibition of cell expansion, a down regulation of TNF receptor expression and inhibited the PMA-induced degranulation of perforin. Taken together these data indicate that PTX is capable of interfering with Vgamm…
Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.
2005
We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.
Characterization of collagenase 3 (matrix metalloproteinase 13) messenger RNA expression in the synovial membrane and synovial fibroblasts of patient…
1999
Objective To study the localization and cell type–specific expression of collagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA). Methods The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase–polymerase chain reaction, and in situ hybridization. Immunohistochemical detection of cell type–specific antigens was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. Results Collagenase 3 mRNA was dete…
Effects of sildenafil on human penile blood vessels.
2000
Abstract Objectives. To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfunction. Methods. Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, and the isometric tension was recorded. We then studied the effects of sildenafil on precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses. Results. Sildenafil (10 −9 to 3 × 10 −6 M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprus…
Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.
1993
1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human…
Relaxation induced by milrinone and rolipram in human penile arteries and veins
2002
Abstract We studied the relaxant effects of milrinone, an inhibitor of phosphodiesterase 3, and rolipram, an inhibitor of phosphodiesterase 4, on contracted human penile dorsal artery and deep dorsal vein. Vascular rings from 12 multi-organ donors were suspended in organ baths for isometric recording of tension. Both milrinone and rolipram inhibited (100%) the contraction induced by noradrenaline and shifted the relaxation–response curves to the cAMP forming agents prostaglandin E1 and forskolin to the left. The findings indicate that the cAMP pathway appears to be a main determinant of relaxation in human penile vessels.
Relaxation of the isolated human internal anal sphincter by sildenafil.
2007
Abstract Background Hypertonicity of the internal anal sphincter (IAS) appears to be involved in the pathogenesis of anal fissure. The relaxant effects of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on isolated human IAS were investigated. Methods The efficacy (maximal effect, Emax) and potency (−log IC50, where IC50 is half-maximal inhibitory concentration) of the PDE5 inhibitors, sildenafil and zaprinast, and of nitric oxide donors, sodium nitroprusside and glyceryl trinitrate, as relaxants of histamine (0·1 mmol/l)-induced tone were examined in IAS strips under isometric contraction. The presence of PDE5 isoenzymes and changes in intracellular calcium and cyclic nucleot…
Vascular Activity of (-)-Anonaine, (-)-Roemerine and (-)-Pukateine, Three Natural 6a(R)-1,2-Methylenedioxyaporphines with Different Affinities for α1…
2004
We have studied the mechanism of action of three 6a( R)-1,2-methylenedioxyaporphines as vasorelaxant compounds. The alkaloids assayed showed different affinities for the three human cloned alpha (1)-adrenoceptor (AR) subtypes stably expressed in rat-1 fibroblasts, showing lower affinity for alpha(1B)-AR with regard to the alpha(1A)- or alpha(1D)-subtypes. These three natural compounds are more potent inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. As all these alkaloids inhibited noradrenaline (NA)-induced [ (3)H]-inositol phosphate formation in cerebral cortex and rat tail artery, they may be safely viewed as alpha (1)-AR antagon…
PHOSPHODIESTERASE INHIBITORS PIROXIMONE AND ENOXIMONE INHIBIT PLATELET AGGREGATION IN VIVO AND IN VITRO
1997
The phosphodiesterase type III inhibitors piroximone (PIR) and enoximone (ENO) exert positive inotropic and vasodilating effects in patients with severe heart failure. PIR and ENO raise cyclic AMP levels in cardiac and vascular smooth muscle cells. Platelet activity is also regulated by intracellular levels of cyclic AMP. In this study we have investigated the effects of PIR and ENO on platelet activity in vivo and in vitro. PIR and ENO inhibited ADP induced platelet aggregation in a time- and concentration-dependent manner with IC50-values of 67 +/- 14 mumol/l and 129 +/- 6 mumol/l, respectively. Coincubation of PIR with the adenylate cyclase activator iloprost resulted in a synergistic po…